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D C Case

Publications and source records attributed to D C Case.

At least 19 recordsLinked to original sources
PubMed1992

Phase II study of intravenous idarubicin in unfavorable non-Hodgkin's lymphoma.

Idarubicin, a new analogue of daunorubicin, was administered i.v. at a dose of 15 mg/m2 to 31 previously treated patients with unfavorable non-Hodgkin's lymphoma. Clinical characteristics included median age, 69 years; performance status, 1; and prior chemotherapeutic regimens, 1. Twenty of the patients were relapsing after prior therapy and 11 were refractory; 29 had received prior anthracycline or anthracenedione. Responses were observed in 43% of patient (3 complete remission and 10 partial remission) with a median duration of 10+ months (2-29+ months). Idarubicin was well tolerated with nonhematological toxicities (nausea/vomiting, mucositis, and anorexia) seen in less than 50% of patients. Median hematological values during the first cycle for this dosage included WBC, 1,300/mm3; platelets, 129,000/mm3; and hemoglobin, 10.9 mg/dl. With dose escalation, hematological toxicity was dose limiting. Symptomatic cardiac toxicity was observed in one patient who had received maximum dose doxorubicin and radiotherapy. Median values for the cardiac ejection fraction during the full course of therapy for the entire group of patients were 0.62 (initial) and 0.60 (final). Idarubicin in i.v. form is an active drug in previously treated patients with unfavorable non-Hodgkin's lymphoma.

Adult↗
PubMed1992

Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia.

The purpose of this study was to determine the relative merits of idarubicin and daunorubicin in acute myeloid leukemia (AML) therapy. Thirty-two sites provided 214 previously untreated adults with AML aged 15 years or more who were randomized to receive for induction therapy cytarabine 100 mg/m2/d as a continuous 7-day infusion plus either daunorubicin 45 mg/m2/d (A + D) or idarubicin 13 mg/m2/d (A + I), daily on the first three days of treatment. Postremission therapy consisted of two courses of the induction regimen at the same daily doses, with the anthracycline administered for 2 days and cytarabine for 5. The complete response (CR) rates for evaluable patients were 70% (A + I) and 59% (A + D) (P = .08). The difference in CR rates was significant in patients aged 18 to 50 years (88% for A + I, 70% for A + D, P = .035). Resistant disease was a significantly more frequent cause of induction therapy failure with A + D than with A + I. Hyperleukocytosis (white blood cell count greater than 50,000/microL) unfavorably affected the attainment of CR with A + D but not with A + I. CR duration was significantly greater after A + I. CR duration was significantly greater after A + I treatment, and the survival of all randomized patients treated with A + I was significantly better than that observed after A + D treatment (median 12.9 months v 8.7 months, respectively, P = .038). Toxicity of the two treatments was similar, although A + I patients experienced more prolonged myelosuppression during consolidation therapy, and a greater incidence of mild chemical hepatitis was observed in the A + I group. It is concluded that, at the doses and schedule used in this study, A + I is superior to A + D for induction therapy of AML in adults.

Adult↗
PubMed1992

Phase II trial of ifosfamide/mesna and mitoxantrone in previously treated patients with non-Hodgkin's lymphoma: cancer and leukemia group B study 8753.

Ifosfamide (2.0 g/m2 intravenously/day x 3) with mesna (400 mg/m2 intravenously q 4 h daily x 3) was combined with mitoxantrone (14 mg/m2 intravenously x 1) and given on a 3 week schedule to patients with previously treated non-Hodgkin's lymphoma. In 45 eligible/evaluable patients, a 47% response rate (95% confidence interval: 32%, 62%) was achieved of which 25% were complete responses and 22% were partial responses. Median duration of remission was 10 months with 42% of patients in remission at 18 months. Hematologic toxicity (granulocytopenia) was the dose-limiting toxicity with severe or life-threatening granulocytopenia in 98% of patients at full protocol doses. Nausea/vomiting was seen in 73% of patients but was usually mild/moderate. Three patients had significant hematuria secondary to ifosfamide. Two patients had severe changes in the left ventricular ejection fraction (LVEF) secondary to mitoxantrone; and one patient had acute neurologic dysfunction secondary to ifosfamide. Ifosfamide/mesna can be safely combined with mitoxantrone at full doses in previously treated patients with non-Hodgkin's lymphoma. This combination should be considered for other trials in lymphoma.

Adult↗
PubMed1992

Phase I-II trial of high-dose melphalan in previously untreated stage III multiple myeloma: Cancer and Leukemia Group B study 8512.

To study the efficiency of high-dose melphalan in previously untreated patients with advanced myeloma, we performed a Phase I-II trial. Twenty-eight patients were treated at dose level of 60-140 mg/m2. Each patient was first treated with a priming dose of cyclophosphamide (300 mg) followed by high-dose melphalen 1 week later. One course of therapy was given. Patients were then followed without further therapy until relapse. Clinical and laboratory features of the 28 patients in this study included: median age 63, performance status 0-2, hypercalcemia 21%, bone pain 82%, paraprotein types: IgG 76%, Iga 20%, and paraproteinuria 71%. Because none of the patients achieved complete remission (CR) at 60 mg/m2, despite life-threatening toxicity in all patients, the dose level was rapidly increased to 140 mg/m2, a dose previously reported to induce a high percentage of CR. At this dose, CR was achieved in only 1 of 11 patients (9%). This patient had multiple plasmacytomas without generalized bone marrow involvement. One additional patient at 100 mg/m2 achieved CR. Of the whole group, 12 achieved PR. Durations of remissions were generally short: CR 6.3 and 18+ months and PR 2.3-18 month, median 6.9 months. Life-threatening myelosuppression was universal with prolonged pancytopenia. Treatment-related deaths from sepsis were observed in 29% of patients. The median survival of the entire group was 15.6 months. Older patients in this trial did not tolerate high-dose melphalen therapy well; this resulted in a high proportion of toxic deaths and poor overall survival.

Adult↗
PubMed1991

Multicenter clinical trial of mitoxantrone in non-Hodgkin's lymphoma and Hodgkin's disease.

In this phase II multicenter trial, the efficacy and safety of mitoxantrone (Novantrone; Lederle Laboratories, Wayne, NJ) were evaluated in the treatment of 206 patients with relapsed non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) previously treated with other agents. Sixty-nine percent of the patients had received prior therapy with doxorubicin. The patients received 14 mg/m2 of mitoxantrone every 3 weeks. Nineteen (12%) of the NHL patients and two (7%) of the HD patients had complete responses (CRs). The combined CR and partial response (PR) rates were 37% (60 of 163) for NHL patients and 36% (10 of 28) for HD patients; the median duration of response was 323 days for NHL patients and 209 days for HD patients. The median survival times were 337 days for patients with NHL and 469 days for patients with HD. The median survival time for patients with low-grade NHL was 589 days compared with 298 days for patients with intermediate-grade NHL and 167 days for patients with high-grade NHL. The median time to treatment failure was 73 days for NHL patients and 98 days for HD patients. The major toxicity was myelosuppression, which was moderate and reversible. Nausea, vomiting, and alopecia were mild. There were two cases of congestive heart failure (CHF) considered related to treatment; both patients had received prior treatment with doxorubicin. In this group of heavily pretreated patients, mitoxantrone was effective and well tolerated. Responses were seen with mitoxantrone in patients who had relapsed after prior therapy with doxorubicin and in patients who had failed to respond to prior therapy with doxorubicin. Mitoxantrone should be evaluated in less heavily pretreated patients and should be considered for incorporation into combination chemotherapeutic regimens for the treatment of malignant lymphoma.

Drug Evaluation↗
PubMed1991

Waldenström's macroglobulinemia: long-term results with the M-2 protocol.

Thirty-three patients with symptomatic Waldenström's macroglobulinemia have been treated with the M-2 protocol (BCNU, cyclophosphamide, vincristine, melphalan, and prednisone). Therapy was administered every 5 weeks for 2 years and every 10 weeks for an additional 1-3 years. Median clinical and laboratory parameters included age 70 years (range 52-87), performance status 1 (1-3), prior therapy 7, weight loss 12, symptomatic hyperviscosity 13, splenomegaly 22, lymphadenopathy 7, hemoglobin 9.6 g/dl (6.7-14.6), IgM paraprotein level 2000 mg% (340-11,600), and serum viscosity 2.1 (1.4-6.0). Responses were observed in 27 patients, of whom 21 were partial responses. Survival ranges from 1 to 120+ months with 58% of patients projected to be alive at 10 years. Twenty-one patients remain alive, of whom 10 are greater than or equal to 6 years from initiation of therapy with M-2. Treatment has been well tolerated with usually only mild to moderate hematologic toxicity. Median nadir white blood cells during the first cycle was 3000/mm3 (1000-5500). Peripheral neuropathy was seen in 54% secondary to vincristine. Nausea/vomiting, anemia requiring transfusions, and alopecia were each noted in approximately 25% of patients. Sepsis was observed in 2 patients. Two characteristics, age and prior therapy, were found to be of borderline statistical significance (p = 0.03) using univariate analysis but were not significant with multivariate analysis. The M-2 protocol may be able to produce prolonged survival in the majority of patients with Waldenström's macroglobulinemia. Additional trials are needed to develop recommendations for therapy as well as factors predictive for survival and suitability for treatment.

Age Factors↗
PubMed1990

Phase II study of oral idarubicin in favorable histology non-Hodgkin's lymphoma.

Idarubicin, a new analogue of daunorubicin, was administered p.o. for 3 consecutive days every 3 weeks at a dose of 45 mg/m2 in 46 patients (45 eligible and evaluable) with previously treated, favorable histology, non-Hodgkin's lymphoma. Median clinical characteristics included an age of 66 years, a performance status of 1, and one prior chemotherapeutic regimen. Forty-one patients were relapsing from prior therapy, and 37 had stage IV disease. Patients with prior anthracycline therapy were excluded. Responses were observed in 58% of patients (10 complete and 16 partial), with a median duration of 6+ months (2-41+ months). Idarubicin was well tolerated. Nonhematological toxicities (nausea/vomiting, mucositis/diarrhea, alopecia, and anorexia) were observed in less than or equal to 50% of patients. Median hematological values during the first cycle include a WBC of 4100/mm3 and a platelet count of 147,000/mm3. With dose escalation, hematological toxicity was the dose-limiting toxicity. Symptomatic cardiac toxicity was not observed. Median values for the resting left ventricular ejection fraction during the course of therapy were 0.65 (initial) and 0.63 (final). Idarubicin in oral form is an active drug in previously treated patients with favorable histology non-Hodgkin's lymphoma.

Administration, Oral↗
PubMed1990

Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia (ANLL). Lederle Cooperative Group.

This phase III, randomized trial in previously untreated adults with ANLL compared mitoxantrone plus cytosine arabinoside with the CALGB "7 + 3" daunorubicin-based regimen. Two hundred evaluable patients (98 treated with the mitoxantrone-based regimen and 102 with the daunorubicin-based regimen) were included in the analysis of efficacy. The median age of the patients was 60 years. The induction regimen comprised cytosine arabinoside 100 mg/m2 by infusion daily for 7 days and mitoxantrone 12 mg/m2 or daunorubicin 45 mg/m2 daily for days 1-3. If needed, a second induction course was administered: cytosine arabinoside for 5 days and mitoxantrone or daunorubicin for 2 days. Postremission therapy consisted of two consolidation courses, identical to the second induction course. Sixty-three percent (62 of 98) of patients treated with mitoxantrone achieved complete remission (CR), compared to 53% (54 of 102) treated with daunorubicin. The median time to CR was 35 days in patients treated with mitoxantrone and 43 days for those treated with daunorubicin. Eighty-nine percent (55 of 62) of patients treated with mitoxantrone who entered complete remission achieved CR following one induction course, compared to 68% (37 of 54) of patients treated with daunorubicin who entered CR. The median duration of CR was 240 days in patients treated with mitoxantrone and 198 days in those treated with daunorubicin; the median length of survival was 328 days in patients who received mitoxantrone and 247 days in those who received daunorubicin. The toxicity profiles in patients treated with either of the two regimens were comparable in incidence and in severity. Patients treated with mitoxantrone required fewer median platelet units and were treated with fewer median days of intravenous antibiotics, compared to those who received daunorubicin. Mitoxantrone in combination with cytosine arabinoside is effective in previously untreated ANLL. complete remissions occur more frequently after a single induction course of the mitoxantrone-based regimen, compared to the standard Cancer and Acute Leukemia Group B regimen. This should be explored in further trials.

Adult↗
PubMed1988

Phase I-II study of epirubicin in multiple myeloma.

Forty patients with relapsed (26) or refractory (14) myeloma were treated with epirubicin of doses of 75, 90, 105, and 120 mg/m2 in groups of 6 or more patients to test for response, maximum tolerated dose, and toxicity. Thirteen patients had received prior doxorubicin and were included in the dose findings part of the study only. Staging was I (1), II (5), and III (34). Partial responses were seen in 5 patients (18.5%) (duration 1.5, 2, 2.5, 10, and 18 months) not previously treated with doxorubicin. No responses were seen in patients treated with prior anthracycline. Responses were not dependent upon dose level of epirubicin. Median nadir white blood cell count at the four-dose levels were 2,300, 1,000, 1,600, and 1,700/mm3 with median nadir granulocyte counts of 897, 720, 688, and 192/mm3. Fever/neutropenia was infrequently observed at the three lower dose levels but occurred in 6 of 10 patients at 120 mg/m2. Platelet nadirs were 110,000, 83,000, 169,000, and 42,000/mm3. Nonhematological toxicity was not dose dependent and included alopecia (100%), nausea/vomiting (40%), and stomatitis (25%). Six patients had greater than or equal to 0.10 changes in the resting ejection fraction with one patient developing congestive heart failure that responded to medical management. This patient had received prior doxorubicin and had a history of myocardial infarction. Epirubicin can produce remissions in patients with previously treated myeloma who have not received prior doxorubicin. Since the response rate was not enhanced at 120/m2 and since fever/neutropenia was seen regularly at this dose level, the recommended dose for further study is 105 mg/m2.

Aged↗
PubMed1988

Phase II trial of ifosfamide and mesna in previously treated patients with non-Hodgkin's lymphoma: Cancer and Leukemia Group B Study 8552.

Ifosfamide (1.25 g/m2 intravenously/day x 5) with mesna (20% of the ifosfamide dose x six doses on each day of ifosfamide therapy) was administered to 46 previously treated patients with non-Hodgkin's lymphoma of which 31 were eligible and evaluable. A 29% response rate (9/31) was observed (2 CR and 7 PR) with a median duration of response of 2.5 months. Myelosuppression was dose-limiting. Hemorrhagic cystitis was observed in three patients (10%). Nausea and vomiting was generally mild or moderate. One patient developed transient neurotoxic symptoms with confusion and disorientation. An additional patient developed an anaphylactic-type reaction with shortness of breath and respiratory strider during the fourth course of therapy. Ifosfamide, as a single agent, produces remissions of limited duration in non-Hodgkin's lymphoma in patients in second or third relapse.

Adolescent↗
PubMed1988

Diffuse well-differentiated lymphocytic lymphoma: chemotherapy with BCNU, cyclophosphamide, vincristine, melphalan and prednisone.

Twenty patients with stage III and IV diffuse well-differentiated lymphocytic lymphoma were treated with combination chemotherapy consisting of BCNU, cyclophosphamide, vincristine, melphalan and prednisone (M-2). Treatment was given every 5 weeks for 11 cycles in responding patients. The median age of the patients was 62 years (range 45-76). There were 12 complete remissions and 6 partial remissions for an overall response rate of 90%. The median duration of remission was 24 months (range 12-79 months) and was identical for complete responders and partial responders. All but 2 responding patients have been subsequently retreated for relapse. The median survival was 84 months (range 1-108 months). Myelosuppression was mild. Nausea/vomiting, neuropathy, alopecia and gastrointestinal symptoms from prednisone were seen in the minority of patients. One patient expired from sepsis/neutropenia during the first cycle of therapy. The M-2 protocol produces effective remissions in diffuse well-differentiated lymphocytic lymphoma. The relapse and survival pattern are similar to the results achieved with other chemotherapy regimens in low-grade lymphoma.

Adult↗
PubMed1987

Phase I-II trial of high-dose epirubicin in patients with lymphoma.

High-dose doxorubicin has shown considerable activity in both previously treated and previously untreated patients with lymphoma. Because of the toxicities of doxorubicin at high dose, we elected to study a new anthracycline at doses comparable to doxorubicin at high dose, to assess response and toxicity. Epirubicin was administered at doses of 120 mg/m2, 150 mg/m2, and 180 mg/m2 every 3 weeks (maximum four doses) to groups of six patients with previously treated intermediate- and high-grade lymphoma. Sixteen of the patients had received significant prior therapy with an anthracycline and/or anthracenedione. At all dose levels, myelosuppression was severe, with median granulocyte nadirs less than 504/mm3. Hematological recovery occurred by day 21 at the 120 mg/m2 and 150 mg/m2 dose levels, allowing for the next cycle of therapy. However, at the 180 mg/m2 dose level, the majority of patients failed to have hematological recovery by the day of the next scheduled therapy. Forty-two % of patients (eight patients) had fever/neutropenia, and required antibiotics. One treatment-related septic death occurred (at 150 mg/m2). Alopecia (68%), fever immediately following treatment (63%), mild/moderate stomatitis (58%), and nausea/vomiting (53%) were the most common nonhematological toxicities. These toxicities were independent of the dose levels and were not dose limiting. A significant change (greater than or equal to 0.10) in the radionuclide ejection (EF) was seen in seven patients. The median of the entire group of patients fell from 0.63 to 0.56. No patient developed clinical or radiological evidence of congestive heart failure. A response rate of 58% (two complete responses, nine partial responses) was achieved with a median duration of 5 months (range, 1-15+). High-dose epirubicin can be successfully utilized in patients with previously treated lymphoma. The only dose-limiting toxicity observed at these dose levels was the lack of hematological recovery by day 21 with 180 mg/m2. Since epirubicin at high dose will be incorporated into high-dose anthracycline regimens in previously untreated patients utilizing a 3-week treatment cycle, 150-180 mg/m2 may be the maximally tolerated dose for such studies.

Adult↗
PubMed1987

Differentiation between essential thrombocythemia and polycythemia vera with marked thrombocytosis.

Accurate distinction between essential thrombocythemia and thrombocytotic polycythemia vera requires determination of the red cell mass in the presence of adequate iron stores, but this is not always possible. We therefore compared the clinical and laboratory features at the time of presentation of 50 patients with unequivocal essential thrombocythemia and 27 patients with thrombocytotic polycythemia vera. Univariate analysis failed to identify any single parameter capable of reliably separating the groups. A logistic regression algorithm incorporating hematocrit, white cell count, and spleen size markedly increased the diagnostic accuracy (92%) compared with predictions based on the hematocrit alone (52%). The algorithm's usefulness for patients with intermediate hematocrits was confirmed by analysis of independent samples of essential thrombocythemia and thrombocytotic polycythemia vera patients, and also by analysis of patients with probable essential thrombocythemia in whom the diagnosis could not be confirmed because of inadequate exclusion of polycythemia vera. Furthermore, comparison of survival data suggests that differentiating these disorders is prognostically important. The algorithm is recommended as an alternate method for differentiating essential thrombocythemia from thrombocytotic polycythemia vera whenever the red cell mass is unavailable or iron deficiency cannot be excluded.

Adult↗
PubMed1987

Interferon alfa-2b/melphalan/prednisone in previously untreated patients with multiple myeloma: a phase I-II trial.

Interferon alfa-2b (Intron A; Schering Plough) has been shown to be active in advanced previously treated multiple myeloma (MM). Recent in vitro evidence has suggested synergy between cytotoxic agents and interferon alfa-2b. This phase I-II protocol was initiated to study interferon alfa-2b in combination with melphalan and prednisone. Groups of five patients received interferon alfa-2b twice-weekly for two weeks at dose levels of 0.5, 1.0, 2.0, 5.0 and 10.0 X 10(6) IU/m2. During week 2, melphalan (9 mg/m2) and prednisone (40 mg/m2) were administered concurrently with interferon alfa-2b followed by a rest period during nadir myelosuppression, the cycles being repeated every 28 days. Thirty patients were entered of whom 21 were Stage III, 3 Stage II and 6 Stage I. Median nadir WBC/mm3 and platelets/mm3 at the various dose levels are given in the table. Serious adverse reactions while on study included myocardial infarction, renal failure and leukopenia-related sepsis. Early response information is available. Twenty-six patients are evaluable for response. Seven have had progressive disease and 19 (69%) a partial response, the median duration was 11+ months. Interferon alfa-2b does not appear to antagonize melphalan/prednisone effectiveness and may be additive or synergistic. Full evaluation of this combination will be undertaken in randomized controlled trials which are now underway.

Acute Kidney Injury↗
PubMed1987

Phase II study of aclarubicin in acute myeloblastic leukemia.

Aclarubicin is a new anthracycline antibiotic that produces substantially less cardiotoxicity in animals that does doxorubicin. Based upon prior Phase I and II trials in leukemia, a Phase II study in acute myeloblastic leukemia was developed to assess the response rate and toxicity in previously treated patients. Forty patients received aclarubicin 100 mg/m2 per day X 3 with repeated course on days 14-16 if marrow hypoplasia was not produced. Complete responses were achieved in 27.5% (11/40) with durations of 1.5, 2, 2, 2, 3, 3+, 4, 5+, 32+, 33+, and 34+ months. Toxic effects of this therapy included severe neutropenia and thrombocytopenia, nausea/vomiting, mucositis, and diarrhea. No patient developed significant changes in the left ventricular ejection fraction, as measured by radionuclide angiography, or any clinical cardiac symptoms. Alopecia was minimal. Aclarubicin can produce a significant response rate in previously treated patients with acute myeloblastic leukemia and should be considered for study in initial therapy.

Aclarubicin↗